Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment
Ana C. deCarvalho,
Amy B. Heimberger,
Erik P Sulman,
Roel G.W. Verhaak
Posted 08 May 2016
bioRxiv DOI: 10.1101/052076 (published DOI: 10.1016/j.ccell.2017.06.003)
Posted 08 May 2016
We leveraged IDH wild type glioblastomas and derivative neurospheres to define tumor-intrinsic transcription phenotypes. Transcriptomic multiplicity correlated with increased intratumoral heterogeneity and tumor microenvironment presence. In silico cell sorting demonstrated that M2 macrophages/microglia are the most frequent type of immune cells in the glioma microenvironment, followed by CD4 T lymphocytes and neutrophils. Hypermutation associated with CD8+ T cell enrichment. Longitudinal transcriptome analysis of 124 pairs of primary and recurrent gliomas showed expression subtype is retained in 53% of cases with no proneural to mesenchymal transition being apparent. Inference of the tumor microenvironment through gene signatures revealed a decrease in invading monocytes but a subtype dependent increase in M2 macrophages/microglia cells after disease recurrence. All expression datasets are accessible through http://recur.bioinfo.cnio.es/.
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